Study objectives and endpoints.

“Investigation of Immune Amnesia Following Measles Infection in Select African Regions” (ClinicalTrials.gov Identifier: NCT06153979) is a prospective, observational, longitudinal study being conducted in two West African countries; Guinea and Mali. Acute measles virus (MeV) infection has been shown to result in a loss of pre-existing immunity (immune amnesia). MeV-induced immune amnesia has not been studied in West Africa where continual MeV outbreaks occur. Additionally previous studies have relied on naturally occurring exposures to viruses to examine the immune systems ability to create antibodies. Thus, the overall goal of this protocol is to investigate the impact of MeV infection on pre-existing immunity to endemic pathogens in West Africa, observe the effect of a subsequent exposure to a novel pathogen (rabies vaccine), and measure the frequency of subsequent healthcare visits. A total of 256 children aged 1–15 years are being enrolled into one of two study arms: those with acute MeV infection (cases) as confirmed by laboratory testing and without (controls). Controls must be immune to MeV (have IgG). Blood samples are collected at multiple time points including screening (Day 0), at an optional visit to repeat IgM serology for inconclusive or negative Day 0 results (Day 7–10), and during follow-up visits on Day 14, Week 13, and Week 52. These blood samples will be tested to evaluate both humoral and cellular immune responses to a panel of viruses, bacteria, and parasites, including pathogens endemic to West Africa. To explore how recent MeV infection may affect the child’s ability to respond to a new exposure, all participants will receive a rabies vaccine (as a controlled stimulus) at one of two timepoints post Day 0 visit. Biological samples will be collected after vaccination to assess if the rabies vaccine response differs: 1) between cases and controls, and 2) based on the time since acute MeV infection. In addition, the study team will collect information on healthcare encounters during the year-long follow-up to determine if there is a difference in the number of encounters by study group. The findings of this study will further the understanding of the MeV immune amnesia phenotype by understanding its impact on endemic pathogens and subsequent immune response following infection.

“特定非洲地区麻疹病毒感染后免疫失忆（immune amnesia）的研究”（美国临床试验数据库（ClinicalTrials.gov）注册号：NCT06153979）是一项在西非两国——几内亚与马里开展的前瞻性、观察性、纵向研究。已有研究证实，急性麻疹病毒（measles virus, MeV）感染可导致预先存在的免疫丧失（即免疫失忆）。但在麻疹持续暴发的西非地区，麻疹病毒诱导的免疫失忆尚未得到相关研究。此外，此前的相关研究多借助病毒的自然暴露来评估免疫系统产生抗体的能力。本研究方案的总体目标为：探究麻疹病毒感染对西非地区地方性病原体预先存在免疫的影响，观察受试者后续暴露于新型病原体（狂犬病疫苗）后的免疫应答变化，并测量后续就医就诊的频率。本研究计划纳入256名1~15岁儿童，分为两个研究队列：经实验室确诊的急性麻疹病毒感染患儿（病例组）及未感染麻疹病毒的儿童（对照组）。对照组需具备麻疹病毒免疫力（血清麻疹免疫球蛋白G（IgG）阳性）。研究将在多个时间点采集血液样本，包括筛查日（第0天）、针对第0天血清学结果不明确或阴性的受试者可选开展免疫球蛋白M（IgM）血清学复检的随访（第7~10天），以及第14天、第13周、第52周的随访访视。上述血液样本将被用于检测机体对一组涵盖病毒、细菌及寄生虫的病原体（包括西非地方性流行病原体）的体液免疫与细胞免疫应答情况。为探究近期麻疹病毒感染如何影响儿童对新型暴露的免疫应答能力，所有受试者将在第0天访视后的两个指定时间点之一接种狂犬病疫苗（作为可控免疫刺激原）。疫苗接种后将采集生物样本，以评估两方面的疫苗应答差异：①病例组与对照组之间的应答差异；②距急性麻疹病毒感染不同时间区间内的应答差异。此外，研究团队将在为期1年的随访期间收集受试者的就医就诊信息，以比较不同研究队列的就诊次数是否存在显著差异。本研究结果将通过阐明麻疹病毒感染对地方性病原体预先免疫的影响及其感染后的后续免疫应答，进一步加深对麻疹病毒诱导免疫失忆表型的理解。